Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Gene expression profiling of colorectal carcinoma

ABSTRACT: To identify the prognostic gene expression markers in early primary colorectal carcinomas, we analyzed genome-wide gene expression profiles using Agilent 4x44K oligonucleotide microarrays. By SVM we selected a gene signature which discriminated patients which later developed metastasis from patients with a good prognosis. Most of the genes that were found to be informative for patients’ distant recurrence were related to the patient’s immune response. Furthermore, our microarray data confirmed the specificity and sensitivity of the angiogenesis-related genes signature. Gene expression profiling of 67 specimens of 55 colorectal carcinomas, 7 normal and 5 adenomas was studied.

ORGANISM(S): Homo sapiens

SUBMITTER: Qing Wang

PROVIDER: E-GEOD-31905 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Angiogenesis inhibitors, such as sunitinib, represent a promising strategy to improve glioblastoma (GBM) tumor response. In this study, we used the O6-methylguanine methyltransferase (MGMT)-negative GBM cell line U87MG stably transfected with MGMT (U87/MGMT) to assess whether MGMT expression affects the response to sunitinib. We showed that the addition of sunitinib to standard therapy (temozolomide [TMZ] and radiation therapy [RT]) significantly improved the response of MGMT positive but not of MGMT-negative cells. Gene expression profiling revealed alterations in the angiogenic profile, as well as differential expression of several receptor tyrosine kinases targeted by sunitinib. MGMT-positive cells displayed higher levels of vascular endothelial growth factor receptor 1 (VEGFR-1) compared with U87/EV cells, whereas they displayed decreased levels of VEGFR-2. Depleting MGMT using O6-benzylguanine suggested that the expression of these receptors was directly related to the MGMT status. Also, we showed that MGMT expression was associated with a dramatic increase in the soluble VEGFR-1/VEGFA ratio, thereby suggesting a decrease in bioactive VEGFA and a shift towards an antiangiogenic profile. The reduced angiogenic potential of MGMT-positive cells is supported by: (i) the decreased ability of their secreted factors to induce endothelial tube formation in vitro and (ii) their low tumorigenicity in vivo compared with the MGMT-negative cells. Our study is the first to show a direct link between MGMT expression and decreased angiogenicity and tumorigenicity of GBM cells and suggests the combination of sunitinib and standard therapy as an alternative strategy for GBM patients with MGMT-positive tumors. RNA was isolated from parental U87 (U87_EV) and MGMT-transfected U87 (U87_MGMT) triplicate. Pairwise gene expression differences were compared between the two cell lines. Features selected had more than 2-fold up-or down-regulated (P values of >05, unpaired Studentâs t-test with Bonferroni multiple testing correction) were identified. Database for annotation, visualization, and integrated discovery23 was used to identify enriched gene ontology (GO) biological themes.24 The GO data mining was conducted at a term specificity level 3.25 The EASE score was set at 0.05 and the minimum number of genes in a category was 5.

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Gene expression profiling of colorectal carcinoma

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